Human papillomaviruses (HPVs) are one the most common sexually transmitted diseases. These[unreadable] small DNA tumor viruses also are the causal agents for virtually all cervical cancers, other[unreadable] anogenital cancers, and a subset of oral cancers. The same subset of 'high risk' HPVs contribute to[unreadable] all of these cancers, with HPV16 being the virus genotype most commonly associated with each[unreadable] cancer. In this project we will determine whether the inhibition of expression of viral genes[unreadable] implicated in an early step of viral infection, the establishment of the viral genome as a nuclear[unreadable] plasmid, can lead to a reduced rate of infection. For these proof of principle studies, we will[unreadable] establish assays for monitoring the effect of siRNAs designed to knockdown expression of relevant[unreadable] papillomaviral genes, optimize the delivery of siRNAs to mucosal epithelia of the female[unreadable] reproductive tract and monitor the efficacy of papillomaviral-specific siRNAs in inhibiting genital[unreadable] infections by Rhesus papillomavirus (RhPV) in its cognate host. RhPV represents the closest[unreadable] animal model virus for studying the infection by anogenital HPVs. From these studies we will learn[unreadable] whether interference with the establishment of the papillomavirus DNA as a replicon in infected[unreadable] cells can reduce the onset of disease.